Elucidating The Mechanisms Of Action Of And Resistance To Endoperoxide Antimalarials
Funder
National Health and Medical Research Council
Funding Amount
$716,755.00
Summary
Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targe ....Artemisinin-based antimalarials (ARTs) save hundreds of thousands of lives every year. Unfortunately resistance of P. falciparum to ART is now emerging in South East Asia and it is critical to know how and why. We will determine what is different about resistant parasites and will develop assays to monitor drug resistance in the field. We have found that the immature form of the malaria parasite is more resistant to ARTs, which helps explain resistance. We will build on this to develop new targetted treatments.Read moreRead less
Breaking Malaria's Lethal Grip: Targeting The Assembly Of An Adhesive Complex On Infected Red Blood Cells
Funder
National Health and Medical Research Council
Funding Amount
$817,426.00
Summary
The malaria parasite, Plasmodium falciparum, infects the red blood cells of its human victims. It causes them to stick to blood vessel walls in the brain, causing severe cerebral complications and death. Adhesion is mediated by a Velcro-like protein that is presented at the red blood cell surface. This project will fully elucidate the pathway for trafficking of the adhesion protein to the red blood cell surface with a view to finding new ways of interfering with malaria disease.
Dissecting The Molecular Basis Of The Malaria Parasite-Erythrocyte Tight Junction Complex
Funder
National Health and Medical Research Council
Funding Amount
$547,356.00
Summary
The parasites that cause malaria disease must invade the human red blood cell to complete their lifecycle. Invasion requires the formation of a complex interface between parasite and red cell called the Tight Junction. However, this structure's molecular makeup is entirely unknown. Our research will use a combination of state-of-the-art microscopy and genetics to define, for the first time, the junction's organization, providing a critical platform for the development of a malaria vaccine.
Trafficking Of The Major Virulence Protein To The Host Cell Surface In Malaria Parasite-infected Erythrocytes
Funder
National Health and Medical Research Council
Funding Amount
$658,164.00
Summary
The malaria parasite infects human red blood cells and causes them to stick to blood vessels in the brain, inducing coma. This causes the deaths of ~2 million children each year. We will use cell biology techniques to manipulate malaria parasites to unravel the details of the molecular ticketing system that the parasite uses to get its adhesive proteins onto the red blood cell surface. The ability to interfere with this process would greatly decrease the impact of this major human pathogen.
Metabolomic Analysis And Membrane Transport Proteins In The Malaria Parasite
Funder
National Health and Medical Research Council
Funding Amount
$368,875.00
Summary
The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the ....The malaria parasite is a single celled organism which invades the red blood cells of those it infects. There is no vaccine and the parasite is becoming increasingly resistant to the drugs that we have available. There is therefore an urgent need for new antimalarial strategies. Research in this area has been helped by the sequencing of the genome of the parasite. However we still don t know what most of the genes in the parasite do, and it is not a straightforward matter to find out. One of the things hampering us in our efforts to develop new antimalarial drugs is our relatively poor understanding of the sorts of biochemical pathways that the parasite relies on to support its high rate of growth and replication inside the red blood cell, as well the biochemical mechanisms that enable it to becomes drug-resistant. In this study we will use a range of modern analytical techniques to carry out the first detailed survey of the biochemical composition - the so-called metabolome - of the parasite. We will investigate how this changes in response to nutrient deprivation, in response to mutations in genes which play a key role in antimalarial drug resistance and in response to changes in the expression of genes encoding proteins which we believe to be involved in the uptake of nutrients by the parasite. This project will provide us with a wealth of new information about the biochemical make-up of the parasite, and it will provide new insights into the biochemical pathways that are operating and which might be targeted with new drugs. The work is likely to provide new insights into mechanisms of antimalarial drug resistance. It will also form the basis for a strategy that is likely to be extremely useful in helping us to ascribe function to the many genes involved in the biochemistry of this important human pathogen.Read moreRead less